Thursday, July 2, 2009

Cathepsin G Peptides

Definition
Cathepsin G peptides are a class of serine proteases that are major components of neutrophil granules1. They are mainly involved in the non-oxidative pathway of intracellular pathogen destruction1.

Discovery
Cathepsins were first purified from calf thymus in 19492. They were identified by their ability to hydrolyze nucleoprotein preparations. Cathepsin G was first purified from human neutrophils in 19823.

Classification
Cathepsin G belongs to the cathepsin family of globular proteases which includes several other members such as cathepsins A, B, C, D and E4.

Structural Characteristics
Cathepsin G is a 26 KDa polypeptide and is folded into two six stranded beta barrels with several alpha helices at the surface5. The N terminus contains a pentapeptide (Ile-Ile-Gly-Gly-Arg) which is important for its antibacterial activity5. It is a very basic peptide since it contains many arginine residues5.

Mode of action
Cathepsin G prefers substrates with a P1 Phe6. It has several substrates including collagen, proteoglycans and angiotensin I 6. It binds to the bacterial surfaces and neutralizes them by its protease action6. The exact mechanism by which it acts is yet to be understood.

Functions
Cathepsin G plays a role in blood clotting as it can inactivate several clotting factors7. It can inhibit the growth of several bacteria including E.coli, P.aeruginosa and S.aureus. Cathepsin G has a number of potential substrates and activities that are difficult to classify, including the conversion of angiotensin I to angiotensin II, the activation and damage of cultured airway epithelial cells, the stimulation of secretion by airway gland serous cells, the induction of transendothelial albumin flux, and the processing of NF-kB (p65) in vitro7. It is not yet clear that any of these activities represent physiologic roles of this enzyme7. It is also known to play an important role in remodeling of tissue during injury or wound7.

References
1.Hanson RD, Connolly NL, Burnett D, Campbell EJ, Senior RM and Ley TJ (1990). Developmental regulation of the human cathepsin G gene in myelomonocytic cells. J. Biol. Chem., 265 (3), 1524-1530.
2.Maver ME and Greco AE (1949). The hydrolysis of nucleoproteins by cathepsins from calf thymus. J. Biol. Chem, 181 (2), 853-860.
3.Tonnesen MG,Klempner MS, Austen KF, and Wintroub BU (1982). Identification of a Human Neutrophil Angiotensin II-generating Protease as Cathepsin G. J. Clin. Invest, 69, 25-30.
4.Rawlings, N.D. and Barrett, A.J. (1994). Families of cysteine proteinases. Methods Enzymol., 244, 461–486.
5.Hof P, Mayr I, Huber R, Korzus E, Potempa J, Travis J, Powers JC, and Bode W (1996). The 1.8 A crystal structure of human cathepsin G in complex with Suc-Val-Pro-PheP-(OPh)2: a Janus-faced proteinase with two opposite specificities. EMBO J, 15(20), 5481–5491.
6.Tanaka T, Minematsu Y, Reilly CF, Travis J, Powers JC (1985). Human leukocyte cathepsin G. Subsite mapping with 4-nitroanilides, chemical modification, and effect of possible cofactors. Biochemistry, 24(8), 2040-7.
7.MacIvor DM, Shapiro SD, Pham CTN, Belaaouaj A, Abraham SN, and Ley TJ (1999). Normal Neutrophil Function in Cathepsin G-Deficient Mice. Blood, 94 (12), 4282-4293.

1 comment:

Nf-kb Signalling System said...

Hello all,

Cathepsin G is an enzymatic protein belonging to the peptidase or protease families. In humans, it is coded by the CTSG gene. The protein encoded by this gene, a member of the peptidase S1 protein family, is found in azurophil granules of neutrophilic polymorphonuclear leukocytes. Thanks a lot!